摘要
目的 建立一套新型的氨基酸残基结构描述符,用此描述符进行多肽的定量构效关系研究。方法 通过理论计算得出 167个氨基酸结构描述参数,再对 167个参数进行主成分分析,从中提取出与氨基酸残基的三维结构性质密切相关的三个结构描述参数c1,c2,c3 scales。然后采用G/PLS算法,建立氨基酸残基结构描述符c scales与多肽生物活性之间的函数关系,确定多肽的QSAR模型。结果 用此方法建立的苦味二肽、ACE抑制剂二肽和缓激肽增效剂五肽的QSAR模型,均有较好的拟合和预测能力,交叉验证相关系数和相关系数都在 0 70以上。结论 氨基酸残基结构描述符c scales能定量的描述氨基酸的三维结构性质,而且利用此描述符能建立预测能力较强的多肽QSAR模型。
Aim To establish a new amino acid structure descriptor that can be applied to polypeptide QSAR studies. Methods The new amino acid structure descriptor c-scales were derived from a principal components analysis of 167 amino acid structure descriptor indexes by theoretic calculation. The c 1,c 2,c 3-scales were related to 3D structural features of amino acid such as steric, electronic and conformation properties etc. G/PLS regression method was used to find out the relationship between the c-scales and the biological activity and developed QSAR models of the polypeptides. Results Using the established method, we developed accordingly QSAR models of Bitter tasting dipeptide, ACE inhibitors and bradykinin-potentiating pentapeptides and their r 2 and XV-r 2 were more than 0.70. Conclusion The c-scales can quantitatively describe the 3D structural features of any coded and non-coded amino acid and can be used to establish a QSAR model of good predictability.
出处
《药学学报》
CAS
CSCD
北大核心
2005年第4期340-346,共7页
Acta Pharmaceutica Sinica
